Optimization of Betulin Colloidal Aqueous Suspension Pretreatment for Determination of Particle Characteristics

Abstract:

Dynamic light scattering (DLS) is a well-established technique to analyze particle size in a liquid medium and sample preparation is an essential step of the analysis to obtain reliable data. In this study, the pretreatment of an aqueous suspension containing betulin particles was studied to characterize the colloidal betulin particles in supramolecular hydrogels obtained by the liquid antisolvent precipitation from purified and unpurified betulin samples. Parameters of two-step homogenization process using rotor and ultrasonic homogenizer, particle concentration, and pH were systematically varied to obtain stable aqueous suspensions that meet the requirements of DLS technique for good particle size analysis. It was found that the purified betulin particles have a higher tendency to agglomerate and their suspension is stable in a narrower concentration and pH range than unpurified. Particle size analysis in suspensions prepared independently shows good reproducibility of sample preparation.

• Periodical: Key Engineering Materials (Volume 933)
• Pages: 147-154
• DOI: https://doi.org/10.4028/p-30e802
• Online since: October 2022
• Authors: Sanita Vitolina*, Aigars Paze, Rudolfs Berzins, Janis Rizhikovs, Raimonds Makars, Daniela Godina, Arturs Teresko
• Keywords: Antisolvent Precipitation, Betulin, Colloidal Suspension, Hydrogel, Particle Size

References

[1] J. Rizhikovs, J. Zandersons, G. Dobele, A. Paze, Isolation of triterpene-rich extracts from outer birch bark by hot water and alkaline pre-treatment or the appropriate choice of solvents, Ind. Crops Prod. 76 (2015) 209-214.

DOI: 10.1016/j.indcrop.2015.06.053

[2] S. Amiri, S. Dastghaib, M. Ahmadi, P. Mehrbod, F. Khadem, H. Behrouj, M.R. Aghanoori, F. Machaj, M. Ghamsari, J. Rosik, A. Hudecki, A. Afkhami, M. Hashemi, M.J. Los, P. Mokarram, T. Madrakian, S. Ghavami, Betulin and its derivatives as novel compounds with different pharmacological effects, Biotechnology Advances 38 (2020) 107409.

DOI: 10.1016/j.biotechadv.2019.06.008

[3] N.A.J.C. Furtado, L. Pirson, H. Edelberg, L.M. Miranda, C. Loira-Pastoriza, V. Preat, Y. Larondelle, C.M. André, Pentacyclic triterpene bioavailability: An overview of in vitro and in vivo studies, Molecules 22(3) (2017) 1-24.

DOI: 10.3390/molecules22030400

[4] E. Liversidge, G. Liversidge. Drug nanoparticles: formulating poorly water-soluble compounds, Toxicologic Pathology 36 (2008) 43-48.

DOI: 10.1177/0192623307310946

[5] U. Bilati, E. Allémann, E Doelker, Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles, Eur. J. Pharm. Sci. 24(1) (2005) 67-75.

DOI: 10.1016/j.ejps.2004.09.011

[6] A.A. Thorat, S.V. Dalvi, Liquid antisolvent precipitation and stabilization of nanoparticles of poorly water soluble drugs in aqueous suspensions: Recent developments and future perspective, Chemical Engineering Journal, 181-182 (2012) 1-34.

DOI: 10.1016/j.cej.2011.12.044

[7] X. Zhao, W. Wang, Y. Zu, Y. Zhang, Y. Li, W. Sun, C. Shan, Y. Ge, Preparation and characterization of betulin nanoparticles for oral hypoglycemic drug by antisolvent precipitation, Drug Deliv. 21(6) (2014) 467-479.

DOI: 10.3109/10717544.2014.881438

[8] B.G. Bag, R. Majumdar, Self-assembly of renewable nano-sized triterpenoids, Chem. Rec. 17 (2017) 1-34.

DOI: 10.1002/tcr.201600123

[9] B.G. Bag, S.S. Dash, Hierarchical self-assembly of a renewable nanosized pentacyclic dihydroxy-triterpenoid betulin yielding flower-like architectures, Langmuir 31(51) (2015) 13664-13672.

DOI: 10.1021/acs.langmuir.5b03730

[10] H.G. Merkus, Particle Size Measurements, Fundamental, Practice, Quality, Springer, Netherlands, Berlin, (2009).

[11] S. Zhang, Q. Zhang, J. Shang, Z. Mao, C. Yang, Measurement methods of particle size distribution in emulsion polymerization, Chinese Journal of Chemical Engineering, 39 (2021) 1-15.

DOI: 10.1016/j.cjche.2021.03.007

[12] P.A. Hassan, S. Rana, G. Verma, Making sense of Brownian motion: colloid characterization by dynamic light scattering, Langmuir 31 (2015) 3-12.

DOI: 10.1021/la501789z

[13] R. Shaw, Dynamic light scattering training - achieving reliable nano particle sizing, information on www.atascientific.com.au.

[14] F.K. Mwiiri, R. Daniels, Optimized birch bark extract-loaded colloidal dispersion using hydrogenated phospholipids as stabilizer, Pharmaceutics 12(9) (2020) 832.

DOI: 10.3390/pharmaceutics12090832

[15] I. Kaur, L.J. Ellis, I. Romer, R. Tantra, M. Carriere, S. Allard, M. Mayne-L'Hermite, C. Minelli, W. Unger, A. Potthoff, S. Rades, E. Valsami-Jones, Dispersion of nanomaterials in aqueous media: towards protocol optimization, J. Vis. Exp. 25(130) (2017) 56074.

DOI: 10.3791/56074

[16] R. Makars, A. Paze, J. Rizikovs, R. Berzins, D. Godiņa, M. Puke, K. Stankus, I. Virsis, Changes in composition of birch outer bark extractives after recrystallization with c2-c5 alkanols, Key Eng. Mater., 850 (2020) 3-8.

DOI: 10.4028/www.scientific.net/kem.850.3

[17] Malvern Instruments Limited, Zetasizer Nano user manual MAN0485(1.1), (2013).